The Mutational Spectrum of Pre- and Post-Neoadjuvant Chemotherapy Triple-Negative Breast Cancers.

The response of triple-negative breast cancer (TNBC) patients to pre-operative (neoadjuvant chemotherapy) is a critical factor of their outcome. To determine the effects of chemotherapy on the tumor genome and to identify mutations associated with chemoresistance and sensitivity, we performed whole exome sequencing on pre/post-chemotherapy tumors and matched lymphocytes from 26 patients. We observed great inter-tumoral heterogeneity with no gene mutated recurrently in more than four tumors besides TP53.

A Call to Action: A Specialty-Specific Course to Support the Next Generation of Clinician Scientists in Anesthesiology.

Clinical production pressure is a significant problem for faculty of anesthesiology departments who seek to remain involved in research. Lack of protected time to dedicate to research and insufficient external funding add to this long-standing issue. Recent trends in funding to the departments of anesthesiology and their academic output validate these concerns.

A Call to Action: A Specialty-Specific Course to Support the Next Generation of Clinician Scientists in Anesthesiology.

Clinical production pressure is a significant problem for faculty of anesthesiology departments who seek to remain involved in research. Lack of protected time to dedicate to research and insufficient external funding add to this long-standing issue. Recent trends in funding to the departments of anesthesiology and their academic output validate these concerns.

Expert Consensus Statement on the Perioperative Management of Adult Patients Undergoing Head and Neck Surgery and Free Tissue Reconstruction From the Society for Head and Neck Anesthesia.

The perioperative care of adult patients undergoing free tissue transfer during head and neck surgical (microvascular) reconstruction is inconsistent across practitioners and institutions. The executive board of the Society for Head and Neck Anesthesia (SHANA) nominated specialized anesthesiologists and head and neck surgeons to an expert group, to develop expert consensus statements. The group conducted an extensive review of the literature to identify evidence and gaps and to prioritize quality improvement opportunities.

Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer.

Response to neoadjuvant chemotherapy (NAC) in triple negative breast cancer (TNBC) is highly prognostic and determines whether adjuvant chemotherapy is needed if residual tumor is found at surgery. To evaluate the predictive and prognostic values of circulating tumor DNA (ctDNA) in this setting, we analyzed tumor and serial bloods from 26 TNBC patients collected prior, during, and after NAC. Individual digital droplet PCR assays were developed for 121 variants (average 5/patient) identified from tumor sequencing, enabling ctDNA detection in 96% of patients at baseline.

Prolonged time to extubation after general anaesthesia is associated with early escalation of care: A retrospective observational study.

Background: Prolonged time to extubation after general anaesthesia has been defined as a time from the end of surgery to airway extubation of at least 15 min. This occurrence can result in ineffective utilisation of operating rooms and delays in patient care. It is unknown if unanticipated delayed extubation is associated with escalation of care.

Erratum: Publisher Correction: Homologous recombination DNA repair defects in -associated breast cancers.

[This corrects the article DOI: 10.1038/s41523-019-0115-9.].

The metabotropic glutamate receptor 5 negative allosteric modulator fenobam: pharmacokinetics, side effects, and analgesic effects in healthy human subjects.

Metabotropic glutamate receptor 5 (mGlu5) has been shown to modulate nociception in animals, but no mGlu5 antagonists have been developed commercially as analgesics. The mGlu5 antagonist fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazole-2-yl)urea] was originally evaluated for development as a nonbenzodiazepine anxiolytic. Fenobam is analgesic in numerous mouse pain models, acting exclusively through mGlu5 blockade.

A Unique Morphological Phenotype in Chemoresistant Triple-Negative Breast Cancer Reveals Metabolic Reprogramming and PLIN4 Expression as a Molecular Vulnerability.

The major obstacle in successfully treating triple-negative breast cancer (TNBC) is resistance to cytotoxic chemotherapy, the mainstay of treatment in this disease. Previous preclinical models of chemoresistance in TNBC have suffered from a lack of clinical relevance. Using a single high dose chemotherapy treatment, we developed a novel MDA-MB-436 cell-based model of chemoresistance characterized by a unique and complex morphologic phenotype, which consists of polyploid giant cancer cells giving rise to neuron-like mononuclear daughter cells filled with smaller but functional mitochondria and numerous lipid droplets.

Precision Medicine Tools to Guide Therapy and Monitor Response to Treatment in a HER-2+ Gastric Cancer Patient: Case Report.

Trastuzumab, has played a major role in improving treatment outcomes in HER-2 positive gastric cancer. However, once there is disease progression there is a paucity of evidence for second line therapy. Patient-derived xenografts (PDXs) in combination with liquid biopsies can help guide individual therapeutic decisions and have now started to be studied.

Homologous recombination DNA repair defects in associated breast cancers.

Mono-allelic germline pathogenic variants in the () gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in -associated breast cancers (BCs), and whether -associated BCs display bi-allelic inactivation of and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic germline mutations were analyzed by whole-exome sequencing (WES,  = 16) or targeted capture massively parallel sequencing (410 cancer genes,  = 8).

A Study of Pre-Analytical Variables and Optimization of Extraction Method for Circulating Tumor DNA Measurements by Digital Droplet PCR.

Background: Circulating free DNA (cfDNA) is an exciting novel method to diagnose, monitor, and predict resistance and response to cancer therapies, with the potential to radically alter the management of cancer patients. To fulfill its potential, greater knowledge about preanalytical variables is required to optimize and standardize the collection process, and maximize the yield and utility of the small quantities of cfDNA extracted.

Methods: To this end, we have compared the cfDNA extraction efficiency of three different protocols, including a protocol developed in house (Jewish General Hospital).

Modifiable and Nonmodifiable Factors Associated With Perioperative Failure of Extraglottic Airway Devices.

Background: Extraglottic airway device (EGA) failure can be associated with severe complications and adverse patient outcomes. Prior research has identified patient- and procedure-related predictors of EGA failure. In this retrospective study, we assessed the incidence of perioperative EGA failure at our institution and identified modifiable factors associated with this complication that may be the target of preventative or mitigating interventions.

Targeted error-suppressed quantification of circulating tumor DNA using semi-degenerate barcoded adapters and biotinylated baits.

Ultrasensitive methods for rare allele detection are critical to leverage the full potential offered by liquid biopsies. Here, we describe a novel molecular barcoding method for the precise detection and quantification of circulating tumor DNA (ctDNA). The major benefits of our design include straightforward and cost-effective production of barcoded adapters to tag individual DNA molecules before PCR and sequencing, and better control over cross-contamination between experiments.

The Estrogen Receptor Cofactor SPEN Functions as a Tumor Suppressor and Candidate Biomarker of Drug Responsiveness in Hormone-Dependent Breast Cancers.

The treatment of breast cancer has benefitted tremendously from the generation of estrogen receptor-α (ERα)-targeted therapies, but disease relapse continues to pose a challenge due to intrinsic or acquired drug resistance. In an effort to delineate potential predictive biomarkers of therapy responsiveness, multiple groups have identified several uncharacterized cofactors and interacting partners of ERα, including Split Ends (SPEN), a transcriptional corepressor. Here, we demonstrate a role for SPEN in ERα-expressing breast cancers.

Bedside predictors of difficult intubation: a systematic review.

Background: Unanticipated difficult intubation is associated with unwanted patient outcomes. The capability of predicting difficult airways may contribute to patient safety, efficient patient flow and rational use of limited resources. We evaluated current literature on performance of bedside airway tests in predicting difficult tracheal intubation.

Mutation analysis of PALB2 in BRCA1 and BRCA2-negative breast and/or ovarian cancer families from Eastern Ontario, Canada.

Background: PALB2 has emerged as a breast cancer susceptibility gene. Mutations in PALB2 have been identified in almost all breast cancer populations studied to date, but the rarity of these mutations and lack of information regarding their penetrance makes genetic counseling for these families challenging. We studied BRCA1/2 -negative breast and/or ovarian cancer families to a) assess the contribution of PALB2 mutations in this series and b) identify clinical, pathological and family history characteristics that might make PALB2 screening more efficient.

Prognosis and patterns of failure for the extubation of patients who remain intubated after head and neck surgery.

Objective: This study aimed to analyze the rate of failure, patterns of failure, and prognostic factors for patients who remain intubated after head and neck surgery and then undergo delayed extubation.

Methods: Retrospective chart review of all otolaryngology patients who remained intubated after head and neck surgery and then underwent delayed extubation between 2006 and 2013. The incidence and patterns of extubation failure were analyzed.